Publications by authors named "Jennifer Wang"

314 Publications

Integrative Clinical and Genomic Characterization of MTAP-deficient Metastatic Urothelial Cancer.

Eur Urol Oncol 2021 Nov 14. Epub 2021 Nov 14.

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Deficiency of MTAP (MTAP) mainly occurs because of homozygous loss of chromosome 9p21, which is the most common copy-number loss in metastatic urothelial cancer (mUC). We characterized the clinical and genomic features of MTAP mUC in 193 patients treated at MD Anderson Cancer Center (MDACC) and 298 patients from the phase 2 IMvigor210 trial, which investigated atezolizumab in cisplatin-ineligible and platinum-refractory disease. In the MDACC cohort, visceral metastases were significantly more common for MTAP (n = 48) than for MTAP-proficient (MTAP; n = 145) patients (75% vs 55.2%; p = 0.02). MTAP was associated with poor prognosis (median overall survival [mOS] 12.3 vs 20.2 mo; p = 0.007) with an adjusted hazard ratio of 1.93 (95% confidence interval 1.35-2.98). Similarly, IMvigor210 patients with MTAP (n = 29) had a higher incidence of visceral metastases than those with MTAP tumors (n = 269; 86.2% vs 72.5%; p = 0.021) and worse prognosis (mOS 8.0 vs 11.3 mo; p = 0.042). Hyperplasia-associated genes were more frequently mutated in MTAP tumors (FGFR3: 31% vs 8%; PI3KCA: 31% vs 19%), while alterations in dysplasia-associated genes were less common in MTAP tumors (TP53: 41% vs 67%; RB1: 0% vs 16%). Our findings support a distinct biology in MTAP mUC that is associated with early visceral disease and worse prognosis. PATIENT SUMMARY: We investigated the outcomes for patients with the most common gene loss (MTAP gene) in metastatic cancer of the urinary tract. We found that this loss correlates with worse prognosis and a higher risk of metastasis in internal organs. There seems to be distinct tumor biology for urinary tract cancer with MTAP gene loss and this could be a potential target for treatment.
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http://dx.doi.org/10.1016/j.euo.2021.10.006DOI Listing
November 2021

Use of Closed Incision Negative Pressure Therapy (ciNPT) in Breast Reconstruction Abdominal Free Flap Donor Sites.

J Clin Med 2021 Nov 5;10(21). Epub 2021 Nov 5.

Department of Plastic and Reconstructive Surgery, Royal Melbourne Hospital, Melbourne, VIC 3050, Australia.

Background: Closed incision negative pressure therapy (ciNPT) may reduce the rate of wound complications and promote healing of the incisional site. We report our experience with this dressing in breast reconstruction patients with abdominal free flap donor sites.

Methods: A retrospective cohort study was conducted of all patients who underwent breast reconstruction using abdominal free flaps (DIEP, MS-TRAM) at a single institution (Royal Melbourne Hospital, Victoria) between 2016 and 2021.

Results: 126 female patients (mean age: 50 ± 10 years) were analysed, with 41 and 85 patients in the ciNPT (Prevena) and non-ciNPT (Comfeel) groups, respectively. There were reduced wound complications in almost all outcomes measured in the ciNPT group compared with the non-ciNPT group; however, none reached statistical significance. The ciNPT group demonstrated a lower prevalence of surgical site infections (9.8% vs. 11.8%), wound dehiscence (4.9% vs. 12.9%), wound necrosis (0% vs. 2.4%), and major complication requiring readmission (2.4% vs. 7.1%).

Conclusion: The use of ciNPT for abdominal donor sites in breast reconstruction patients with risk factors for poor wound healing may reduce wound complications compared with standard adhesive dressings; however, large scale, randomised controlled trials are needed to confirm these observations. Investigation of the impact of ciNPT patients in comparison with conventional dressings, in cohorts with equivocal risk profiles, remains a focus for future research.
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http://dx.doi.org/10.3390/jcm10215176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584502PMC
November 2021

Definitive radiotherapy in lieu of systemic therapy for oligometastatic renal cell carcinoma: a single-arm, single-centre, feasibility, phase 2 trial.

Lancet Oncol 2021 Oct 27. Epub 2021 Oct 27.

Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: The role of radiotherapy in metastatic renal cell carcinoma is controversial. We prospectively tested the feasibility and efficacy of radiotherapy to defer systemic therapy for patients with oligometastatic renal cell carcinoma.

Methods: This single-arm, phase 2, feasibility trial was done at one centre in the USA (The MD Anderson Cancer Center, Houston, TX, USA). Patients (aged ≥18 years) with five or fewer metastatic lesions, an Eastern Cooperative Oncology Group status of 0-2, and no more than one previous systemic therapy (if this therapy was stopped at least 1 month before enrolment) without limitations on renal cell carcinoma histology were eligible for inclusion. Patients were treated with stereotactic body radiotherapy (defined as ≤5 fractions with ≥7 Gy per fraction) to all lesions and maintained off systemic therapy. When lesion location precluded safe stereotactic body radiotherapy, patients were treated with hypofractionated intensity-modulated radiotherapy regimes consisting of 60-70 Gy in ten fractions or 52·5-67·5 Gy in 15 fractions. Additional rounds of radiotherapy were allowed to treat subsequent sites of progression. Co-primary endpoints were feasibility (defined as all planned radiotherapy completed with <7 days unplanned breaks) and progression-free survival. All efficacy analyses were intention-to-treat. Safety was analysed in the as-treated population. A second cohort, with the aim of assessing the feasibility of sequential stereotactic body radiotherapy alone in patients with low-volume metastatic disease, was initiated and will be reported separately. This study is registered with ClinicalTrials.gov, NCT03575611.

Findings: 30 patients (six [20%] women) were enrolled from July 13, 2018, to Sept 18, 2020. All patients had clear cell histology and had a nephrectomy before enrolment. All patients completed at least one round of radiotherapy with less than 7 days of unplanned breaks. At a median follow-up of 17·5 months (IQR 13·2-24·6), median progression-free survival was 22·7 months (95% CI 10·4-not reached; 1-year progression-free survival 64% [95% CI 48-85]). Three (10%) patients had severe adverse events: two grade 3 (back pain and muscle weakness) and one grade 4 (hyperglycaemia) adverse events were observed. There were no treatment-related deaths.

Interpretation: Sequential radiotherapy might facilitate deferral of systemic therapy initiation and could allow sustained systemic therapy breaks for select patients with oligometastatic renal cell carcinoma.

Funding: Anna Fuller Foundation, the Cancer Prevention and Research Institute of Texas (CPRIT), and the National Cancer Institute.
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http://dx.doi.org/10.1016/S1470-2045(21)00528-3DOI Listing
October 2021

Type I IFN-Driven Immune Cell Dysregulation in Rat Autoimmune Diabetes.

Immunohorizons 2021 10 26;5(10):855-869. Epub 2021 Oct 26.

Department of Medicine, University of Massachusetts Medical School, Worcester, MA;

Type 1 diabetes is a chronic autoimmune disease, characterized by the immune-mediated destruction of insulin-producing β cells of pancreatic islets. Essential components of the innate immune antiviral response, including type I IFN and IFN receptor (IFNAR)-mediated signaling pathways, likely contribute to human type 1 diabetes susceptibility. We previously showed that LEW.1WR1 rats have a significant reduction in diabetes frequency following Kilham rat virus (KRV) infection. To delineate the impact of IFNAR loss on immune cell populations in KRV-induced diabetes, we performed flow cytometric analysis in spleens from LEW.1WR1 wild-type (WT) and rats after viral infection but before the onset of insulitis and diabetes. We found a relative decrease in CD8 T cells and NK cells in KRV-infected LEW.1WR1 rats compared with KRV-infected WT rats; splenic regulatory T cells were diminished in WT but not rats. In contrast, splenic neutrophils were increased in KRV-infected rats compared with KRV-infected WT rats. Transcriptional analysis of splenic cells from KRV-infected rats confirmed a reduction in IFN-stimulated genes in compared with WT rats and revealed an increase in transcripts related to neutrophil chemotaxis and MHC class II. Single-cell RNA sequencing confirmed that MHC class II transcripts are increased in monocytes and macrophages and that numerous types of splenic cells harbor KRV. Collectively, these findings identify dynamic shifts in innate and adaptive immune cells following IFNAR disruption in a rat model of autoimmune diabetes, providing insights toward the role of type I IFNs in autoimmunity.
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http://dx.doi.org/10.4049/immunohorizons.2100088DOI Listing
October 2021

Abnormal Paraoxonase-1 (PON1) enzyme activity in idiopathic inflammatory myopathies.

Rheumatology (Oxford) 2021 Oct 26. Epub 2021 Oct 26.

Divisions of Rheumatology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.

Objectives: Patients with idiopathic inflammatory myopathies (IIM) have severe vascular involvement, which contributes to disease morbidity and mortality. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL) associated protein, which protects the vascular endothelium from oxidative injury and damage. The current work assessed the functional and genetic determinants of PON1 activity in IIM patients.

Methods: 184 IIM patients and 112 healthy controls (HC) were included. PON1 enzyme activity was assessed by paraoxonase, arylesterase and lactonase assays, and the Q192R PON1 single nucleotide polymorphism (SNP) was analyzed. Multivariate regression models examined associations of PON1 activity with IIM diagnosis and myositis disease outcomes.

Results: The arylesterase and lactonase activities of PON1 were significantly lower in IIM patients compared with HC. Higher myositis disease activity, the presence of severe IIM associated interstitial lung disease (ILD), and the presence of MDA5 or anti-synthetase antibodies were significantly associated with lower PON1 activity. The PON1 Q192R polymorphism was strongly linked to the paraoxonase activity of PON1 in IIM, and patients with the PON1 QQ genotype had better IIM disease outcomes compared with patients with the QR or RR genotypes.

Conclusions: The arylesterase and lactonase activities of PON1 are significantly impaired in IIM patients compared with HC, and inversely associate with IIM disease activity and the presence of severe ILD. The PON1 QQ genotype associates with more favorable disease outcomes in IIM patients. Large prospective studies are needed to further evaluate the role of PON1 and PON1 genetic polymorphisms in the development and propagation of IIM and IIM-ILD.
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http://dx.doi.org/10.1093/rheumatology/keab795DOI Listing
October 2021

Chronic obstructive pulmonary disease risk assessment tools: is one better than the others?

Curr Opin Pulm Med 2021 Oct 13. Epub 2021 Oct 13.

Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Purpose Of Review: Risk assessment tools are essential in COPD care to help clinicians identify patients at higher risk of accelerated lung function decline, respiratory exacerbations, hospitalizations, and death.

Recent Findings: Conventional methods of assessing risk have focused on spirometry, patient-reported symptoms, functional status, and a combination of these tools in composite indices. More recently, qualitatively and quantitatively assessed chest imaging findings, such as emphysema, large and small airways disease, and pulmonary vascular abnormalities have been associated with poor long-term outcomes in COPD patients. Although several blood and sputum biomarkers have been investigated for risk assessment in COPD, most still warrant further validation. Finally, novel remote digital monitoring technologies may be valuable to predict exacerbations but their large-scale performance, ease of implementation, and cost effectiveness remain to be determined.

Summary: Given the complex heterogeneity of COPD, any single metric is unlikely to fully capture the risk of poor long-term outcomes. Therefore, clinicians should review all available clinical data, including spirometry, symptom severity, functional status, chest imaging, and bloodwork, to guide personalized preventive care of COPD patients. The potential of machine learning tools and remote monitoring technologies to refine COPD risk assessment is promising but remains largely untapped pending further investigation.
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http://dx.doi.org/10.1097/MCP.0000000000000833DOI Listing
October 2021

Human nasal wash RNA-Seq reveals distinct cell-specific innate immune responses in influenza versus SARS-CoV-2.

JCI Insight 2021 11 22;6(22). Epub 2021 Nov 22.

Department of Medicine and.

BACKGROUNDInfluenza A virus (IAV) and SARS-CoV-2 are pandemic viruses causing millions of deaths, yet their clinical manifestations are distinctly different.METHODSWith the hypothesis that upper airway immune and epithelial cell responses are also distinct, we performed single-cell RNA sequencing (scRNA-Seq) on nasal wash cells freshly collected from adults with either acute COVID-19 or influenza or from healthy controls. We focused on major cell types and subtypes in a subset of donor samples.ResultsNasal wash cells were enriched for macrophages and neutrophils for both individuals with influenza and those with COVID-19 compared with healthy controls. Hillock-like epithelial cells, M2-like macrophages, and age-dependent B cells were enriched in COVID-19 samples. A global decrease in IFN-associated transcripts in neutrophils, macrophages, and epithelial cells was apparent in COVID-19 samples compared with influenza samples. The innate immune response to SARS-CoV-2 appears to be maintained in macrophages, despite evidence for limited epithelial cell immune sensing. Cell-to-cell interaction analyses revealed a decrease in epithelial cell interactions in COVID-19 and highlighted differences in macrophage-macrophage interactions for COVID-19 and influenza.ConclusionsOur study demonstrates that scRNA-Seq can define host and viral transcriptional activity at the site of infection and reveal distinct local epithelial and immune cell responses for COVID-19 and influenza that may contribute to their divergent disease courses.FundingMassachusetts Consortium on Pathogen Readiness, the Mathers Foundation, and the Department of Defense (W81XWH2110029) "COVID-19 Expansion for AIRe Program."
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http://dx.doi.org/10.1172/jci.insight.152288DOI Listing
November 2021

Next-generation sequencing confirms T-cell clonality in a subset of pediatric pityriasis lichenoides.

J Cutan Pathol 2021 Oct 6. Epub 2021 Oct 6.

Department of Dermatology, Stanford University Medical Center, Stanford, California, USA.

Background: Pityriasis lichenoides (PL) is a papulosquamous disease that affects both adults and children. Previous studies have shown a subset of this entity to have clonal T-cell populations via PCR-based assays. In this study, we sought to implement next-generation sequencing (NGS) as a more sensitive and specific test to examine for T-cell clonality within the pediatric population.

Methods: We identified 18 biopsy specimens from 12 pediatric patients with clinical and histopathologic findings compatible with PL. Patient demographics, clinical features, management, and histopathologic findings were reviewed. All specimens were analyzed for clonality with NGS of T-cell receptor beta (TRB) and gamma (TRG) genes.

Results: Of the 12 patients, 9 (75%) had complete resolution of lesions at the time of data collection (mean follow-up 31 months). The remaining three patients significantly improved with methotrexate (with or without acitretin). Interestingly, 7 of 12 patients (58%) and 9 of 17 biopsy specimens (53%) showed evidence of T-cell clonality. Two patients showed matching TRB clones from different anatomic sites.

Conclusions: T-cell clonality is a common finding in PL, probably representing a "reactive clonality" rather than a true lymphoproliferative disorder. Clonality alone cannot be used as a means to distinguish PL from lymphomatoid papulosis or cutaneous lymphoma.
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http://dx.doi.org/10.1111/cup.14143DOI Listing
October 2021

Abiraterone acetate plus prednisone in non-metastatic biochemically recurrent castration-naïve prostate cancer.

Eur J Cancer 2021 11 15;157:259-267. Epub 2021 Sep 15.

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Background: Intermittent androgen deprivation therapy (ADT) in biochemically recurrent castration-naïve prostate cancer is non-inferior to continuous therapy. We hypothesised that finite-duration abiraterone acetate plus prednisone (Abi +P) added to ADT will further reduce the duration of treatment exposure by prolonging time to prostate-specific antigen (PSA) recurrence without impacting eugonad state recovery.

Methods: This phase II, randomised, open-label trial enrolled patients with rising PSA ≥ 0.2 ng/ml after radical prostatectomy and/or a PSA ≥ 1 following radiotherapy. Patients were randomised 1:1 to receive Abi (1 g PO daily) + P (5 mg PO daily) + ADT or ADT alone for 8 months. The primary end-point was PSA-free survival difference at 1 year following completion of therapy.

Results: Between February 2013 and July 2016, 200 patients were enrolled. Of 100 patients randomised to each arm, 99 in the Abi +P arm and 98 in the ADT arm were evaluable. Median follow-up was 64.4 months. Median PSA-free survival was 27.0 months for the Abi +P-treated group versus 19.9 months for the ADT-treated group (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.47-0.87). The PSA-free survival at 1 year post-treatment completion was 98% for the Abi +P group and 88% for the ADT group. Median time to eugonad state was 13.1 months for the abiraterone-treated group and 12.8 months for the ADT-treated group. Median eugonad PSA-free survival was 12.5 months for the abiraterone-treated group versus 9.0 for the ADT-treated group (HR 0.72, 95% CI 0.53-0.98). There were no significant between-group differences in androgen deprivation-related adverse events.

Conclusions: In men with biochemically recurrent prostate cancer following definitive treatment of the primary, finite duration treatment with ADT and Abi +P results in a significantly longer PSA relapse-free interval than treatment with ADT alone.
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http://dx.doi.org/10.1016/j.ejca.2021.06.017DOI Listing
November 2021

Safety Matters: A Meta-analysis of Interhospital Transport Adverse Events in Critically Ill Patients.

Air Med J 2021 Sep-Oct;40(5):350-358. Epub 2021 May 24.

Research Associate Program, Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD; Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD; Program in Trauma, R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD. Electronic address:

Objective: Interhospital transport (IHT) is common among critically ill patients. Our meta-analysis investigated the prevalence and possible factors associated with adverse events (AEs) during IHT.

Methods: Searching PubMed, Embase, and Scopus databases until February 12, 2021, we included studies that a priori defined AEs for adult medical patients. We excluded case reports, non-full-text, and non-English language studies. We performed a random effects meta-analysis and moderator analyses.

Results: We identified 554 studies and included 19 studies (14,969 patients) in our final analysis. The mean patients' (standard deviation) age was 60 (13.7). The pooled medical AEs for IHT was 1,059 (11%, 95% confidence interval, 7.5%-16%). The most common AE (n, %) was hypotension (424, 2.8%). Moderator analyses and meta-regressions suggested that conditions (P < .001) such as respiratory failure from coronavirus infection (88%), stroke (19%), and the need for extracorporeal membrane oxygenation (40%) were associated with higher AE prevalence. Transport by nurses (31%) and physicians (11%) was associated with a higher AE prevalence, whereas transport type did not influence AE prevalence.

Conclusion: Our study suggests the prevalence of AEs of critically ill patients during IHT is low and likely due to patients' disease severity. Further studies should focus on interventions to mitigate AEs to improve patients' outcomes.
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http://dx.doi.org/10.1016/j.amj.2021.04.008DOI Listing
November 2021

Prevalence of myocardial infarction among patients with chest pain and cocaine use: A systematic review and meta-analysis.

Am J Emerg Med 2021 Aug 19;50:428-436. Epub 2021 Aug 19.

Research Associate Program in Emergency Medicine and Critical Care, The R Adams Cowley Shock Trauma Center, University of Maryland School of Maryland, Baltimore, MD, USA; Department of Emergency Medicine, University of Maryland School of Maryland, Baltimore, MD, USA; Program in Trauma, The R Adams Cowley Shock Trauma Center, University of Maryland School of Maryland, Baltimore, MD, USA. Electronic address:

Background: Cocaine abuse is a public health burden. Cocaine is known to cause vasospasm and acute myocardial infarction (AMI). The prevalence of AMI in patients presenting with chest pain and concurrent cocaine use (CPCC) varies among studies. We performed a systemic review and meta-analysis to assess the current literature for the prevalence of AMI in patients with CPCC.

Methods: We performed a literature search of PubMed, EMBASE, and Scopus from its beginning to May 18, 2020 and updated this search on February 18, 2021. Full-text studies that assessed the primary outcome (AMI) specifically among patients with CPCC who presented to the emergency department (ED) were included. We excluded studies that were not in English, did not take place in the ED, and case reports, which only reported positive cases and not incidence of AMI. Random effect meta-analysis was performed to assess the prevalence of primary outcome and to examine correlations between risk factors and AMI. Heterogeneity was assessed by I-square value. We also performed subgroup analysis to identify potential sources of heterogeneity.

Results: We identified 2178 studies and screened 102 full-text studies to include 16 studies (3269 patients) in our final analysis. The pooled prevalence of AMI was 4.7% (95% CI 0.8-23), I-square of 84%. However, rates among studies of low risk patients were lower (1.1% 95% CI 0.2-5) compared to studies of mixed risk patients (7.7%, 95% 5-11). A meta-regression was used to look at correlation between risk factors and AMI and found that AMI was positively correlated in patients with a history of CAD (correlation coefficient [Corr. Coeff.] 5.6, 96% CI 2.3-8.7), HTN (Corr. Coeff. 2.9, 95% CI 0.9-4.9), DM (Corr. Coeff. 8.0, 95% CI 2.4-14), HLD (Corr. Coeff. 5.9, 95% CI 2.4, 9). Sources of potential heterogeneity included patients' risk as defined by the authors, study designs, publication year, and study sample size.

Conclusion: The overall prevalence of AMI and death among patients with cocaine-associated chest pain was relatively low, although high risk patients were still associated with high prevalence of AMI. Clinicians should consider risk-stratify these patients and treat them accordingly.
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http://dx.doi.org/10.1016/j.ajem.2021.08.024DOI Listing
August 2021

Substance use, depression, and loneliness among American veterans during the COVID-19 pandemic.

Am J Addict 2021 11 19;30(6):552-559. Epub 2021 Aug 19.

Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Background And Objectives: Behavioral health issues, such as substance use, depression, and social isolation, are of grave concern during COVID-19, especially for vulnerable populations. One such population is US veterans, who have high rates of pre-existing behavioral health conditions and may thus be at-risk for poorer outcomes. The current study aimed to investigate substance use among US veterans during COVID-19 as a function of pre-existing depression, loneliness, and social support.

Methods: We investigated the relationship between pre-pandemic depression and substance use during COVID-19 using linear (alcohol) and logistic (cannabis) regression among a large sample of US veterans (N = 1230). We then tested if loneliness and social support moderated these effects.

Results: Though there was a decrease in alcohol and cannabis use among the overall sample, veterans who screened for depression prior to the pandemic exhibited higher levels of substance use after the pandemic's onset. Loneliness compounded the effects of depression on rates of alcohol use. Social support was not protective for the effects of depression on either alcohol or cannabis use.

Discussion And Conclusions: Veterans with pre-existing depression may be in need of attention for substance use behaviors. Interventions aimed at alleviating loneliness among veterans may be useful in mitigating alcohol use, but not cannabis use, amid COVID-19.

Scientific Significance: Our findings are among the first to report tangible behavioral health outcomes experienced by US veterans as a result of COVID-19. Results can help inform treatment efforts for veterans who are struggling with substance use during and post-pandemic.
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http://dx.doi.org/10.1111/ajad.13211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441617PMC
November 2021

The Mount Sinai Hospital Institute for critical care medicine response to the COVID-19 pandemic.

Acute Crit Care 2021 Aug 10;36(3):201-207. Epub 2021 Aug 10.

Institute for Critical Care Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: The coronavirus disease 2019 (COVID-19) pandemic resulted in a surge of critically ill patients. This was especially true in New York City. We present a roadmap for hospitals and healthcare systems to prepare for a Pandemic.

Methods: This was a retrospective review of how Mount Sinai Hospital (MSH) was able to rapidly prepare to handle the pandemic. MSH, the largest academic hospital within the Mount Sinai Health System, rapidly expanded the intensive care unit (ICU) bed capacity, including creating new ICU beds, expanded the workforce, and created guidelines.

Results: MSH a 1,139-bed quaternary care academic referral hospital with 104 ICU beds expanded to 1,453 beds (27.5% increase) with 235 ICU beds (126% increase) during the pandemic peak in the first week of April 2020. From March to June 2020, with follow-up through October 2020, MSH admitted 2,591 COVID-19-positive patients, 614 to ICUs. Most admitted patients received noninvasive support including a non-rebreather mask, high flow nasal cannula, and noninvasive positive pressure ventilation. Among ICU patients, 68.4% (n=420) received mechanical ventilation; among the admitted ICU patients, 42.8% (n=263) died, and 47.8% (n=294) were discharged alive.

Conclusions: Flexible bed management initiatives; teamwork across multiple disciplines; and development and implementation of guidelines were critical accommodating the surge of critically ill patients. Non-ICU services and staff were deployed to augment the critical care work force and open new critical care units. This approach to rapidly expand bed availability and staffing across the system helped provide the best care for the patients and saved lives.
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http://dx.doi.org/10.4266/acc.2021.00402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435441PMC
August 2021

Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse events.

J Immunother Cancer 2021 07;9(7)

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Background: Immune checkpoint therapy (ICT) prolongs survival in subsets of patients with cancer but can also trigger immune-related adverse events (irAEs) requiring treatment discontinuation. Recent studies have investigated safety of ICT rechallenge after irAEs, and evidence suggests that rechallenge may be associated with improved antitumor responses. However, data are limited on response duration after ICT rechallenge, particularly after severe irAEs.

Objective: To evaluate safety and efficacy of ICT rechallenge after moderate-to-severe irAEs in patients with renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer.

Methods: In this retrospective cohort study, medical records from September 25, 2013, to June 1, 2020, for patients with genitourinary (GU) cancers at MD Anderson Cancer Center who were rechallenged with the same or different ICT following irAEs were reviewed. Demographics, ICT exposure, irAEs (grade and treatment), ICT discontinuation or rechallenge, rates of subsequent irAEs (new or recurrent) and antitumor activity (objective response rates and response duration) were reviewed.

Results: Sixty-one patients with RCC, UC, and prostate cancer were rechallenged with ICT after experiencing 105 total irAEs. Objective response rates after rechallenge, that is, upgrade in response, were 14% in RCC (4/28), 21% in UC (3/14), and 0% in prostate cancer. All seven patients who achieved upgrade in response had initial grade 2 or 3 irAEs. Responses were durable among these seven patients, with median radiographic progression-free survival not reached (range: 3.7-66.4 months) as of the March 8, 2021, data cut-off (median follow-up 40.9 months (95% CI 35.3 to 46.5)). All achieved complete response except one patient who was lost to follow-up. The rate of subsequent grade 3 or 4 irAEs after rechallenge was 30%, with no fatal irAEs. The rate of recrudescence of the same irAE was 26% (16/61). 54% of patients received corticosteroids (33/61), and 21% received targeted immunosuppression (13/61) for the initial irAEs.

Conclusions And Relevance: ICT rechallenge after moderate-to-severe irAEs was associated with deep and durable responses in a subset of patients with RCC and UC, with acceptable safety and no fatal events. Strategies to enable ICT resumption after moderate-to-severe irAEs, such targeted immunosuppression, warrant further study.
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http://dx.doi.org/10.1136/jitc-2021-002850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323401PMC
July 2021

Cuticular hydrocarbons are associated with mating success and insecticide resistance in malaria vectors.

Commun Biol 2021 07 26;4(1):911. Epub 2021 Jul 26.

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Anopheles coluzzii females, important malaria vectors in Africa, mate only once in their lifetime. Mating occurs in aerial swarms with a high male-to-female ratio, where traits underlying male mating success are largely unknown. Here, we investigated whether cuticular hydrocarbons (CHCs) influence mating success in natural mating swarms in Burkina Faso. As insecticides are widely used in this area for malaria control, we also determined whether CHCs affect insecticide resistance levels. We find that mated males have higher CHC abundance than unmated controls, suggesting CHCs could be determinants of mating success. Additionally, mated males have higher insecticide resistance under pyrethroid challenge, and we show a link between resistance intensity and CHC abundance. Taken together, our results suggest that CHC abundance may be subject to sexual selection in addition to selection by insecticide pressure. This has implications for insecticide resistance management, as these traits may be sustained in the population due to their benefits in mating even in the absence of insecticides.
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http://dx.doi.org/10.1038/s42003-021-02434-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313523PMC
July 2021

SARS-CoV-2 Initiates Programmed Cell Death in Platelets.

Circ Res 2021 09 23;129(6):631-646. Epub 2021 Jul 23.

Department of Medicine, Division of Cardiovascular Medicine (M.K., H.A.C., O.V., K.T., J.R., J.E.F.), University of Massachusetts Medical School, Worcester, MA.

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCRESAHA.121.319117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409903PMC
September 2021

Management of Anaplastic and Recurrent Differentiated Thyroid Cancer: Indications for Surgical Resection, Molecular Testing, and Systemic Therapy.

Neuroimaging Clin N Am 2021 Aug;31(3):359-366

Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Differentiated and anaplastic thyroid cancer are tumors derived from follicular thyroid cancers and are clinically and genetically distinct. Treatment of these tumors has evolved over the past decade, with 6 drugs/drug combinations that are US Food and Drug Administration approved.
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http://dx.doi.org/10.1016/j.nic.2021.04.005DOI Listing
August 2021

Imaging of Cervical Lymph Nodes in Thyroid Cancer: Ultrasound and Computed Tomography.

Neuroimaging Clin N Am 2021 Aug;31(3):313-326

Department of Neuroradiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1482, Houston, TX 77030-4009, USA. Electronic address:

Sonographic evaluation of cervical lymph nodes in patients with thyroid malignancy is important both for preoperative staging and for post-treatment surveillance, and contrast-enhanced computed tomography plays a complementary role. Knowledge of anatomy and surgical approaches, combined with an understanding of the various imaging features that distinguish malignant from benign lymph nodes, allows for accurate staging, thereby enabling complete surgical initial resection.
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http://dx.doi.org/10.1016/j.nic.2021.04.002DOI Listing
August 2021

A laser platform incorporating a novel 524 nm laser pumped by a commercial hair removal laser effectively treats facial redness and lower-extremity spider veins.

Lasers Surg Med 2021 Jul 7. Epub 2021 Jul 7.

Candela Inc., Wayland, Massachusetts, USA.

Background And Objectives: Treatment of vascular lesions is one of the main applications of cutaneous laser technology, while the other is laser hair removal. We present here a vascular laser pumped by a commercial hair removal laser.

Study Design/materials And Methods: A novel 524 nm vascular laser was designed using a 755 nm hair removal laser as a pumping source. This 524 nm vascular laser was used to treat facial redness and leg telangiectasias in 24 subjects. Four treatments were administered to the face at 4-6-week intervals and final photographs were taken 8 weeks following the final treatment, while two treatments were administered to lower-extremity spider veins at 2-month intervals with follow-up photographs 3 months following the final treatment. Blinded analysis of digital images was performed by two physicians not involved in the study.

Results: Blinded evaluation of digital photographs revealed an average improvement score of 3.3 ± 1.7 (mean ± SEM) on a 0-10 scale for removing facial redness (p < 0.001), representing a 33% improvement. Leg veins improved an average of 51% corresponding to a score of 5.1 ± 2.0 (p < 0.001). Side effects were mild and limited to erythema, purpura, edema, and one instance of mild hyperpigmentation.

Conclusions: This novel 524 nm laser is safe and effective for treating vascularity on the face and legs, and proves the ability to create a laser platform incorporating a hair removal laser which then can be used as a pumping source for the attached vascular laser module.
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http://dx.doi.org/10.1002/lsm.23451DOI Listing
July 2021

Definitive radiotherapy for extracranial oligoprogressive metastatic renal cell carcinoma as a strategy to defer systemic therapy escalation.

BJU Int 2021 Jul 6. Epub 2021 Jul 6.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Objective: To study whether delivering definitive radiotherapy (RT) to sites of oligoprogression in metastatic renal cell carcinoma (mRCC) enabled deferral of systemic therapy (ST) changes without compromising disease control or survival.

Patients And Methods: We identified patients with mRCC who received RT to three or fewer sites of extracranial progressive disease between 2014 and 2019 at a large tertiary cancer centre. Inclusion criteria were: (1) controlled disease for ≥3 months before oligoprogression, (2) all oligoprogression sites treated with a biologically effective dose of ≥100 Gy, and (3) availability of follow-up imaging. Time-to-event end-points were calculated from the start of RT.

Results: A total of 72 patients were identified (median follow-up 22 months, 95% confidence interval [CI] 19-32 months), with oligoprogressive lesions in lung/mediastinum (n = 35), spine (n = 30), and non-spine bone (n = 5). The most common systemic therapies before oligoprogression were none (n = 33), tyrosine kinase inhibitor (n = 23), and immunotherapy (n = 13). At 1 year, the local control rate was 96% (95% CI 87-99%); progression-free survival (PFS), 52% (95% CI 40-63%); and overall survival, 91% (95% CI 82-96%). At oligoprogression, ST was escalated (n = 16), maintained (n = 49), or discontinued (n = 7), with corresponding median (95% CI) PFS intervals of 19.7 (8.2-27.2) months, 10.1 (6.9-13.2) months, and 9.8 (2.4-28.9) months, respectively. Of the 49 patients maintained on the same ST at oligoprogression, 21 did not subsequently have ST escalation.

Conclusion: Patients with oligoprogressive mRCC treated with RT had comparable PFS regardless of ST strategy, suggesting that RT may be a viable approach for delaying ST escalation. Randomised controlled trials comparing treatment of oligoprogression with RT vs ST alone are needed.
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http://dx.doi.org/10.1111/bju.15541DOI Listing
July 2021

Patient-reported menstrual and obstetric outcomes following hysteroscopic adhesiolysis for Asherman syndrome.

F S Rep 2021 Mar 11;2(1):118-125. Epub 2021 Jan 11.

Newton Wellesley Hospital, Center for Minimally Invasive Gynecologic Surgery, Newton, Massachusetts.

Objective: Review the menstrual and obstetric outcomes among Asherman syndrome patients when stratified by disease severity.

Design: Retrospective cohort study.

Setting: A community teaching hospital affiliated with a large academic medical center.

Patients: A total of 355 Asherman syndrome patients stratified by March classification who underwent hysteroscopic adhesiolysis.

Interventions: Telephone survey, analyzed with multivariable analysis.

Main Outcome Measures: Return of menstruation. Pregnancy, miscarriage, and live birth rate.

Results: A total of 355 patients underwent hysteroscopic adhesiolysis. Of these, 150 (42.3%) patients completed the telephone survey with a mean follow-up of 2.21 years. Additionally, 40.7% had mild, 52.7% had moderate, and 6.6% had severe disease. Furthermore, 25.3% of patients reported amenorrhea at presentation, with mild disease patients having the highest rate of returning menstruation (93.8%) following treatment. The cumulative pregnancy rate was 81.9%, and the cumulative live birth rate was 51.2%, with no statistical differences identified by the classification group.

Conclusion: Asherman syndrome disease severity predicted returning menstruation but not pregnancy or live birth rate.
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http://dx.doi.org/10.1016/j.xfre.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244383PMC
March 2021

Novel Anaplastic Thyroid Cancer PDXs and Cell Lines: Expanding Preclinical Models of Genetic Diversity.

J Clin Endocrinol Metab 2021 Oct;106(11):e4652-e4665

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Context: Anaplastic thyroid cancer (ATC) is a rare, aggressive, and deadly disease. Robust preclinical thyroid cancer models are needed to adequately develop and study novel therapeutic agents. Patient-derived xenograft (PDX) models may resemble patient tumors by recapitulating key genetic alterations and gene expression patterns, making them excellent preclinical models for drug response evaluation.

Objective: We developed distinct ATC PDX models concurrently with cell lines and characterized them in vitro and in vivo.

Methods: Fresh thyroid tumor from patients with a preoperative diagnosis of ATC was surgically collected and divided for concurrent cell line and PDX model development. Cell lines were created by generating single cells through enzymatic digestion. PDX models were developed following direct subcutaneous implantation of fresh tumor on the flank of immune compromised/athymic mice.

Results: Six ATC PDX models and 4 cell lines were developed with distinct genetic profiles. Mutational characterization showed one BRAF/TP53/CDKN2A, one BRAF/CDKN2A, one BRAF/TP53, one TP53 only, one TERT-promoter/HRAS, and one TERT-promoter/KRAS/TP53/NF2/NFE2L2 mutated phenotype. Hematoxylin-eosin staining comparing the PDX models to the original patient surgical specimens show remarkable resemblance, while immunohistochemistry stains for important biomarkers were in full concordance (cytokeratin, TTF-1, PAX8, BRAF). Short tandem repeats DNA fingerprinting analysis of all PDX models and cell lines showed strong concordance with the original tumor. PDX successful establishment rate was 32%.

Conclusion: We have developed and characterized 6 novel ATC PDX models with 4 matching cell lines. Each PDX model harbors a distinct genetic profile, making them excellent tools for preclinical therapeutic trials.
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http://dx.doi.org/10.1210/clinem/dgab453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530744PMC
October 2021

Systemic Therapy for Hepatocellular Carcinoma.

Clin Liver Dis (Hoboken) 2021 May 4;17(5):337-340. Epub 2021 Jun 4.

Division of Gastroenterology, Hepatology, and Nutrition Department of Internal Medicine University of Chicago Medicine Chicago IL.

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http://dx.doi.org/10.1002/cld.1058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177835PMC
May 2021

"Raising HOPE": Improved Outcomes for HIV/HCV-coinfected Liver Transplant Recipients in the Direct-acting Antiviral Era.

Transplant Direct 2021 Jul 8;7(7):e707. Epub 2021 Jun 8.

Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, TX.

The 2013 HIV Organ Policy Equity Act has increased liver transplantation (LT) in HIV patients; however, transplant centers may remain reluctant to perform LT in HIV/hepatitis C virus (HCV)-coinfected patients due to inferior outcomes. We aimed to assess how direct-acting antivirals (DAAs) have impacted HIV/HCV-coinfected LT recipient outcomes.

Methods: national data including 70 125 adult LT recipients between 2008 and 2019 were analyzed. Kaplan-Meier survival analysis and Cox proportional hazards model were used to analyze outcomes.

Results: LT for HIV individuals increased in the DAA era from 28 in 2014 to 64 in 2019 (23 had HIV/HCV coinfection). In the pre-DAA era, HIV/HCV-coinfected LT recipients had an increased risk of graft failure compared with HIV/HCV-uninfected LT recipients (hazard ratio [HR], 1.85;  < 0.001). In contrast, there was no difference in graft failure between HIV/HCV-coinfected versus HIV/HCV-uninfected LT recipients in the DAA era (HR, 1.24;  = 0.308). Among coinfected LT recipients in the DAA era, 1- and 3-y cumulative graft survivals were 88.6% and 81.7% compared with 76.3% and 58.0% in the pre-DAA era, respectively ( = 0.006). In Cox analysis, HCV coinfection was not associated with graft failure (HR, 1.00; 95% confidence interval, 0.53-1.89) among HIV LT recipients in the DAA era (n = 271). Black and Hispanic populations accounted for almost half of HIV/HCV LTs in the DAA era.

Conclusions: HIV/HCV-coinfected LT recipient outcomes have improved significantly in the DAA era. Our results should offer reassurance to transplant centers and encourage timely transplantation referral of HIV patients with decompensated cirrhosis, including patients coinfected with HCV.
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http://dx.doi.org/10.1097/TXD.0000000000001154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191686PMC
July 2021

Dermatology Advances Into an Era of Precision Medicine.

JAMA Dermatol 2021 Jul;157(7):770-772

Department of Dermatology, Stanford University School of Medicine, Stanford, California.

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http://dx.doi.org/10.1001/jamadermatol.2021.0024DOI Listing
July 2021

MIF is a 3' flap nuclease that facilitates DNA replication and promotes tumor growth.

Nat Commun 2021 05 19;12(1):2954. Epub 2021 May 19.

Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.

How cancer cells cope with high levels of replication stress during rapid proliferation is currently unclear. Here, we show that macrophage migration inhibitory factor (MIF) is a 3' flap nuclease that translocates to the nucleus in S phase. Poly(ADP-ribose) polymerase 1 co-localizes with MIF to the DNA replication fork, where MIF nuclease activity is required to resolve replication stress and facilitates tumor growth. MIF loss in cancer cells leads to mutation frequency increases, cell cycle delays and DNA synthesis and cell growth inhibition, which can be rescued by restoring MIF, but not nuclease-deficient MIF mutant. MIF is significantly upregulated in breast tumors and correlates with poor overall survival in patients. We propose that MIF is a unique 3' nuclease, excises flaps at the immediate 3' end during DNA synthesis and favors cancer cells evading replication stress-induced threat for their growth.
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http://dx.doi.org/10.1038/s41467-021-23264-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134555PMC
May 2021

Hepatobiliary Manifestations of Short Bowel Syndrome and Intestinal Failure-Associated Liver Disease.

Clin Liver Dis (Hoboken) 2021 Apr 1;17(4):297-300. Epub 2021 May 1.

Department of Internal Medicine Section of Gastroenterology, Hepatology and Nutrition University of Chicago Medicine Chicago IL.

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http://dx.doi.org/10.1002/cld.1053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087921PMC
April 2021

"Unresectable" polyp management utilizing advanced endoscopic techniques results in high rate of colon preservation.

Surg Endosc 2021 Apr 22. Epub 2021 Apr 22.

Division of Colorectal Surgery, Department of Surgery, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.

Purpose: "Endoscopically unresectable" benign polyps identified during screening colonoscopy are often referred for segmental colectomy. Application of advanced endoscopic techniques can increase endoscopic polyp resection, sparing patients the morbidity of colectomy. This retrospective case-control study aimed to evaluate the success of colon preserving resection of "endoscopically unresectable" benign polyps using advanced endoscopic techniques including endoscopic mucosal resection, endoscopic submucosal dissection, endoluminal surgical intervention, full-thickness laparo-endoscopic excision, and combined endo-laparoscopic resection.

Methods: A prospectively maintained institutional database identified 95 patients referred for "endoscopically unresectable" benign polyps from 2015 to 2018. Cases were compared to 190 propensity score matched controls from the same database undergoing elective laparoscopic colectomy for other reasons. Primary outcome was rate of complete endoscopic polyp removal. Secondary outcomes included length of stay, unplanned 30-day readmission and reoperation, 30-day mortality, and post-procedural complications.

Results: Advanced endoscopic techniques achieved complete polyp removal without colectomy in 66 patients (70%). Failure was most commonly associated with previously attempted endoscopic resection and occult malignancy. Compared with matched colectomy controls, endoscopic polyp resection resulted in significantly shorter hospital length of stay (1.13 ± 2.41 vs 3.89 ± 4.57 days; p < 0.001), lower unplanned 30-day readmission (1.1% vs 7.7%; p < 0.05), and fewer postoperative complications (4.2% vs 33.9%; p < 0.001). Unplanned 30-day reoperation (2.1% vs 4.4%; p = 0.34) and 30-day mortality (0% vs 0.6%; p = 0.75) trended lower.

Conclusions: Endoscopic resection of complex polyps can be highly successful, and it is associated with favorable outcomes and decreased morbidity when compared with segmental colon resection. Attempting colon preservation using these techniques is warranted.
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http://dx.doi.org/10.1007/s00464-021-08499-7DOI Listing
April 2021

Clinical Characterization of Mogamulizumab-Associated Rash During Treatment of Mycosis Fungoides or Sézary Syndrome.

JAMA Dermatol 2021 Jun;157(6):700-707

Department of Dermatology, Stanford University School of Medicine, Palo Alto, California.

Importance: Mogamulizumab is a monoclonal antibody against CCR4 approved for treatment for mycosis fungoides (MF) and Sézary syndrome (SS). Mogamulizumab-associated rash (MAR) is difficult to differentiate from cutaneous MF or SS, which can lead to unnecessary discontinuation of drug use because of concern for severe drug reaction or incorrect presumption of disease relapse or progression in the skin.

Objective: To examine the most common clinical presentations of MAR in patients with MF or SS and the diagnostic and management challenges.

Design, Setting, And Participants: This retrospective case series assessed patients from a multidisciplinary cutaneous lymphoma clinic and supportive oncodermatology clinic at a major academic referral center who had a diagnosis of MF or SS and received mogamulizumab from January 1, 2013, to January 1, 2020. Treatment was followed by new or worsening rash with skin biopsy results compatible with drug eruption determined by clinicopathologic correlation and molecular testing to exclude active malignant disease.

Exposures: At least 1 dose of mogamulizumab.

Main Outcomes And Measures: Mogamulizumab-associated rash was characterized by clinical features, including time to onset, clinical presentation, histopathologic features, and management approach.

Results: The study included 19 patients with MF or SS who developed MAR (median age, 65 years; age range, 38-82 years; 10 [52.6%] male). Median time to MAR onset was 119 days (range, 56 days to 3.8 years). Patients with MAR exhibited 4 predominant clinical presentations: (1) folliculotropic MF-like scalp plaques with alopecia, (2) papules and/or plaques, (3) photoaccentuated dermatitis, and (4) morbilliform or erythrodermic dermatitis. The most common anatomical region involved was the head and neck, including the scalp. Histopathologic findings were variable and did not correspond to primary clinical morphologic findings. Immunohistochemistry and T-cell clonality ancillary testing were helpful to distinguish MAR from disease. Most patients with MAR (14 of 19) discontinued mogamulizumab treatment; however, no life-threatening severe cutaneous adverse drug reactions occurred, and the decision for drug therapy cessation was usually multifactorial. Four patients were treated again with mogamulizumab with no life-threatening drug-related events. Approaches to management of MAR include topical corticosteroids, systemic corticosteroids, and/or methotrexate.

Conclusions And Relevance: This case series found that mogamulizumab-associated rash had a heterogeneous clinical presentation with variable and delayed onset in patients with MF or SS. Mogamulizumab-associated rash exhibited a predilection for the head and neck and was difficult to clinically distinguish from relapse or progression of disease. Recognition of the most common clinical presentations can help prevent unnecessary discontinuation of mogamulizumab treatment. The presence of MAR does not necessitate permanent discontinuation of or avoidance of retreatment with mogamulizumab.
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http://dx.doi.org/10.1001/jamadermatol.2021.0877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060888PMC
June 2021
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